Document Detail

Invariant natural killer T cells: linking inflammation and neovascularization in human atherosclerosis.
MedLine Citation:
PMID:  21061446     Owner:  NLM     Status:  MEDLINE    
Atherosclerosis, a chronic inflammatory lipid storage disease of large arteries, is complicated by cardiovascular events usually precipitated by plaque rupture or erosion. Inflammation participates in lesion progression and plaque rupture. Identification of leukocyte populations involved in plaque destabilization is important for effective prevention of cardiovascular events. This study investigates CD1d-expressing cells and invariant NKT cells (iNKT) in human arterial tissue, their correlation with disease severity and symptoms, and potential mechanisms for their involvement in plaque formation and/or destabilization. CD1d-expressing cells were present in advanced plaques in patients who suffered from cardiovascular events in the past and were most abundant in plaques with ectopic neovascularization. Confocal microscopy detected iNKT cells in plaques, and plaque-derived iNKT cell lines promptly produced proinflammatory cytokines when stimulated by CD1d-expressing APC-presenting α-galactosylceramide lipid antigen. Furthermore, iNKT cells were diminished in the circulating blood of patients with symptomatic atherosclerosis. Activated iNKT cell-derived culture supernatants showed angiogenic activity in a human microvascular endothelial cell line HMEC-1-spheroid model of in vitro angiogenesis and strongly activated human microvascular endothelial cell line HMEC-1 migration. This functional activity was ascribed to IL-8 released by iNKT cells upon lipid recognition. These findings introduce iNKT cells as novel cellular candidates promoting plaque neovascularization and destabilization in human atherosclerosis.
Emmanouil Kyriakakis; Marco Cavallari; Jan Andert; Maria Philippova; Christoph Koella; Valery Bochkov; Paul Erne; S Brian Wilson; Lucia Mori; Barbara C Biedermann; Therese J Resink; Gennaro De Libero
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-27
Journal Detail:
Title:  European journal of immunology     Volume:  40     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-09     Completed Date:  2010-12-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  3268-79     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Laboratory for Signal Transduction, Department of Biomedicine, Basel University Hospital, Basel, Switzerland.
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MeSH Terms
Aged, 80 and over
Antigens, CD1d / biosynthesis,  immunology
Arteries / immunology,  metabolism,  pathology
Atherosclerosis / immunology*,  metabolism,  pathology
Cell Line
Cell Movement / immunology*
Cytokines / biosynthesis,  immunology
Endothelial Cells / immunology*,  metabolism,  pathology
Gene Expression Regulation / immunology
Inflammation / immunology,  metabolism,  pathology
Inflammation Mediators / immunology,  metabolism
Natural Killer T-Cells / immunology*,  metabolism,  pathology
Neovascularization, Pathologic / immunology*,  metabolism,  pathology
Reg. No./Substance:
0/Antigens, CD1d; 0/CD1D protein, human; 0/Cytokines; 0/Inflammation Mediators

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